Endoscopic ultrasound (EUS) has evolved from a purely diagnostic to an interventional modality offering minimally invasive alternatives to surgical and radiologic interventions. This has led to a rapidly growing interest in EUS-guided vascular interventions. EUS-guided portal venous access is an emerging technique which opens a new arena for interventional vascular EUS. Portal vein can be accessed under EUS guidance with high precision and low risk of complications thus expanding its application for both benign and malignant conditions. Potential applications of EUS-guided portal vein access include: fine needle aspiration of portal vein thrombus and portal venous blood sampling for circulating tumor cells for diagnosis and staging of occult and known malignancies; portal vein angiography, portal pressure measurement, and creation of endoscopic intrahepatic portosystemic shunt; portal vein embolization and targeted drug delivery. This article will review the current literature on EUS-guided portal vein access, its feasibility and safety in animal and human studies, and current diagnostic and therapeutic applications with future directions.